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Blood, 1 February 2005, Vol. 105, No. 3, pp. 1337-1342. Prepublished online as a Blood First Edition Paper on September 30, 2004; DOI 10.1182/blood-2004-07-2966. This Article Full Text (PDF) All Versions of this Article: 2004-07-2966v1 105/3/1337    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mims, M. P Articles by Prchal, J. T Search for Related Content PubMed PubMed Citation Articles by Mims, M. P Articles by Prchal, J. T Related Collections Related Article in Blood Online Related Letter in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 2, 2004 Accepted September 20, 2004 Identification of a human mutation of DMT1 in a patient with microcytic anemia and iron overload Martha P Mims, Yongli Guan, Dagmar Pospisilova, Monika Priwitzerova, Karel Indrak, Prem Ponka, Vladimir Divoky, and Josef T Prchal* Division of Hematology/Oncology, Baylor College of Medicine and Houston VA Medical Center, Houston, Texas, USA Department of Pediatrics, Faculty of Medicine Palacky University, Olomouc, Czech Republic Department of Biology, Faculty of Medicine Palacky University, Olomouc, Czech Republic Department of Hemato-oncology, Faculty of Medicine Palacky University, Olomouc, Czech Republic McGill University, Montreal, Canada Department of Biology, Faculty of Medicine Palacky University, Olomouc, Czech Republic; Department of Hemato-oncology, Faculty of Medicine Palacky University, Olomouc, Czech Republic * Corresponding author; email: jprchal{at}bcm.tmc.edu. Divalent metal transporter 1 (DMT1) is a transmembrane protein crucial for duodenal iron absorption and erythroid iron transport. DMT1 function has been elucidated largely in studies of the mk mouse and the Belgrade rat which have an identical single nucleotide mutation of this gene which affects protein processing, stability and function. These animals exhibit hypochromic microcytic anemia due to impaired intestinal iron absorption, and defective iron utilization in red cell precursors. We report here the first human mutation of DMT1 identified in a female with severe hypochromic microcytic anemia and iron overload. This homozygous mutation in the ultimate nucleotide of exon 12 codes for a conservative Glu 399 to Asp amino acid substitution, however; its predominant effect is preferential skipping of exon 12 during processing of pre-messenger RNA. The lack of full length mRNA would predict deficient iron absorption in the intestine and deficient iron utilization in erythroid precursors; however, unlike the animal models of DMT1 mutation, the patient is iron overloaded. This does not appear to be due to upregulation of total DMT1 mRNA. DMT1 protein is easily detectable by immunoblotting in the patient's duodenum, but it is unclear whether the protein is properly processed or targeted. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: DMT1 mutations: mice and humans are not alike Clara Camaschella Blood 2005 105: 916-917. [Full Text] [PDF] Related Letter in Blood Online: Analysis of the E399D mutation in SLC11A2 Hiromi Gunshin, Jie Jin, Yuko Fujiwara, Nancy C. Andrews, Martha Mims, and Josef Prchal Blood 2005 106: 2221-2222. [Full Text] [PDF] This article has been cited by other articles: S. Soe-Lin, S. S. Apte, B. Andriopoulos Jr., M. C. Andrews, M. 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